Up to 30 percent of postpartum women develop depressive symptoms and 14% develop major or minor depression. Although relationships between thyroid status and depression are well established in the general population and large thyroid changes occur during and following pregnancy, there have been few studies of thyroid function in pre or postpartum (perinatal) depression. We found robustly significant correlations between low, euthyroid range total and free thyroxine (TT4, FT4) concentrations during late pregnancy and higher perinatal depression self-ratings. Postpartum TSH levels fell significantly in mothers with low depression but did not decline and were significantly more elevated in mothers who were more depressed. A significantly higher fraction of mothers with depression history had lower prepartum TT4 & FT4 concentrations. We will test the validity of our findings in a larger cohort (N = 200), determine if lower late pregnancy TT4 & FT4 levels are also related to perinatal syndromal (major or minor) depression or anxiety symptoms or disorders, ascertain whether lower prepartum TT4 & FT4 levels are related to depression history and test whether prenatal thyroid measures improve prediction of postpartum depression especially when combined with known risk factors (abuse history, stressful life events, low social support). We hypothesize that perinatal depression is related to greater sensitivity to suppression of the HPT axis by sex hormone and possibly cortisol elevations during pregnancy producing lower prepartum TT4 & FT4 levels. This results in a surge of central drive in the HPT axis after the rapid postpartum drop in these hormone levels producing higher postpartum TSH levels. Indices of increased central drive in the HPT axis (elevated CSF TRH concentrations, blunted TSH release by TRH) are associated with major depression. To test our theory, we will determine if lower antenatal TT4 & FT4 levels are significantly related to higher postpartum TSH levels and if that relationship is associated with perinatal depression. We will also examine if there are interactions between late pregnancy sex hormone and cortisol levels and late pregnancy TT4 & FT4 levels in predicting perinatal depression. PUBLIC HEALTH RELEVANCE: About 14% of mothers develop clinical depression within the first 3 months after giving birth and a similar percentage become depressed during pregnancy. This project is based on two preliminary studies that found that mothers who are more depressed postpartum have relatively low (but normal range) thyroid hormone levels during late pregnancy but then have higher levels of other thyroid hormones after giving birth. The goals of this project are to see if these results are confirmed in a much larger number of pregnant and postpartum women, if thyroid hormone levels during late pregnancy might help predict which mothers will become depressed, if pre or postpartum thyroid measures are related to anxiety symptoms or disorders (which are also common in the postpartum period) and to test a theory about how lower late pregnancy thyroid hormone levels might contribute to postpartum depression.